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There was a gap of six years between Till Death Do Us Part and Rise Up, the longest between studio albums of Cypress Hill's recording career at the time of release. The group commenced work on the record in 2005, but had not entered studio work until 2008.[5] The writing and recording process spanned four years and a number of recording studios and was finished in 2009.

Rise Up was delayed several times before its release. Originally scheduled to be released in 2006, it was later postponed to March 23, 2010 (exactly six years since the release of their last album), then again to April 6. The album's release date was finally set for April 20, 2010.

In terms of the album's musical direction, in March 2010 Cypress Hill emcee B-Real told noted UK urban writer Pete Lewis - Deputy Editor of the award-winning Blues & Soul - "Musically we wanted a bigger sound, a more AGGRESSIVE sound, and something obviously with a lotta DYNAMICS. You know, our sound has always been raw and gritty, ominous and moody... And, while this time we still wanted it to be raw and dark, we also wanted it to be more UPTEMPO. Because, in terms of the live setting, whenever we do songs that are more uptempo and aggressive people do love them and it makes for a great SHOW. So, while making this album, we definitely had the intention of making songs that would translate well to the live aspect of what Cypress Hill is about. So that, when we play these songs out, we're gonna get a magnificent reaction from the crowd!"[6]

Rise Up marks a major shift in the group's sound, as it was the first of their albums not produced by founding member DJ Muggs. While Muggs does contribute co-production with DJ Khalil on two songs, B-Real takes on the role as main producer, executive producer and overseer of the project. Other producers include Mike Shinoda of Linkin Park, Jim Jonsin, Pete Rock, Jake One, Sick Jacken and Tom Morello.

The album's introduction single, "It Ain't Nothin'" was released as a free download from the group's official website with a music video by Matt Alonzo. "Rise Up", with Tom Morello, is the second single; it also features as the theme song for Elimination Chamber 2010 and the end-credit track for the Season 3 finale episode of the television show Silicon Valley.

PopMatters said, "As much as B-Real still seems lively, Sen Dog seems to have smoked himself out of being a rapper. He sounds exhausted and unimaginative all over this record. He doesn’t even appear on all of the tracks. This imbalance, coupled with the array of random producers, causes an inconsistency in the LP’s sound that hurts Rise Up."[11]

An early review, Scottish magazine The Skinny offered a largely positive 3 stars (out of 5), noting that the album appears "less playful than its predecessor (2004’s Clash-sampling Till Death Do Us Part) but surprisingly more focused - given Muggs’ notable absence from the producer's chair – [The Hill] source inspired collaborations with Pete Rock, Jim Jonsin and Marc Anthony to reinforce their timeless agenda."

Rise Up debuted on the Billboard 200 on April 28 at #19 selling 18,000 copies.[14] The next week it fell over 50 spots to #72 on the Top 200 albums.[15] In its third week the album fell off the Top 100 to #105 and has sold 31,000 copies to date.[16]